6-35944187-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052961.4(SLC26A8):​c.2626C>G​(p.Leu876Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC26A8
NM_052961.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.928
Variant links:
Genes affected
SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10407144).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC26A8NM_052961.4 linkc.2626C>G p.Leu876Val missense_variant Exon 20 of 20 ENST00000490799.6 NP_443193.1 Q96RN1-1A0A024RCV0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC26A8ENST00000490799.6 linkc.2626C>G p.Leu876Val missense_variant Exon 20 of 20 1 NM_052961.4 ENSP00000417638.1 Q96RN1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2626C>G (p.L876V) alteration is located in exon 20 (coding exon 19) of the SLC26A8 gene. This alteration results from a C to G substitution at nucleotide position 2626, causing the leucine (L) at amino acid position 876 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Uncertain
0.059
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;.;T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.70
.;T;T
M_CAP
Uncertain
0.24
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Uncertain
-0.027
T
MutationAssessor
Uncertain
2.0
M;.;M
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.2
N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.013
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.12
B;B;B
Vest4
0.12
MutPred
0.20
Gain of loop (P = 0.0435);.;Gain of loop (P = 0.0435);
MVP
0.49
MPC
0.55
ClinPred
0.15
T
GERP RS
-0.94
Varity_R
0.064
gMVP
0.073

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35911964; API